Tesofensine (NS2330) is a serotonin–noradrenaline–dopamine reuptake inhibitor or also known as triple reuptake inhibitor, which means that it inhibits the reabsorption of the neurotransmitters (brain chemicals) serotonin, norepinephrine, and dopamine. This process increases the extracellular concentrations of these neurotransmitters. The therapeutic benefits of tesofensine are attributed to this effect because each of these neurotransmitters exerts an important function at different locations in the brain.

Overall Health Benefits of Tesofensine

  • Fights Obesity [6-21]
  • Improves Cognitive Health [23-30]
  • Improves Mood [31-33]
  • Improves Blood Sugar Levels [34-36]
  • Increases Energy Levels [37]
  • Treats Sexual Dysfunction [38]
  • Treats Eating Disorders [39-42]
  • Treats Attention-Deficit/Hyperactivity Disorder (ADHD) [43-45]
  • Improves Sleep Quality [46-53]
  • Fights Alcohol Addiction [54-58]

Fights Obesity

Tesofensine is widely known as a weight loss drug. Researchers believe that tesofensine may help treat obese and overweight patients because it boosts the levels of dopamine in the brain. A deficiency in this neurotransmitter has been shown to be linked with overeating and obesity. [1-5] An overwhelming body of human studies supports the fat-burning effect of tesofensine:

  1. The results of the 2018 phase 3 Viking study showed that obese patients who received both doses of oral tesofensine (0.25 and 0.50 mg once daily) had statistically and clinically significant weight loss with low incidence of adverse events at week 24. [6]
  2. The results of Phase 2b trial (TIPO-1) showed that obese patients treated with tesofensine lost an average of 12.8 kg on the 1 mg dose, 11.3 kg on the 0.5 mg dose and 6.7 kg on the 0.25 mg dose, compared with a 2.2 kg loss in the placebo group, suggesting that tesofensine has the potential to produce a weight loss twice that of currently approved drugs. [7]
  3. In the TIPO-2 trial, tesofensine administration in obese patients reduced their desire to eat and increased their satiety levels after 14 days of treatment. [8]
  4. Preliminary results of the TIPO-4 trial, a 48-week open-label extension to the TIPO-1 trial, showed that patients continuing with 0.5mg oral tesofensine achieved a total mean weight loss of 13–14kg at 24 weeks. [9]
  5. In obese patients, tesofensine treatment at varying doses (0.25 mg, 0.5 mg or 1.0 mg) resulted in statistically significant and clinically relevant weight loss with positive effects on energy balance, appetite, physical activity, and quality of life. [10]
  6. In obese patients, tesofensine administration at a dose of 0.5 mg for 26 weeks produced weight loss twice that of anti-obesity agents such as sibutramine or rimonabant. [11]
  7. In overweight patients, tesofensine administration for 24 weeks is associated with enhanced appetite suppression and significant weight loss. [12]
  8. In phase II clinical trials with tesofensine in obese individuals, significant reductions in body weight, body fat and waist circumference were observed without any adverse side effects. [13]
  9. In obese patients, long-term tesofensine supplementation is well-tolerated and resulted in significant weight loss. [14]
  10. In patients with Parkinson’s or Alzheimer’s disease, tesofensine administration once daily for 14 weeks without any weight loss program induced weight loss of approximately 4%, which is similar to that of sibutramine. [15]
  11. In healthy males, multiple administration of tesofensine at doses of 0.125–1 mg induced a significant increase in dopamine levels, resulting in appetite suppression. [16]
  12. In diet-induced obese rat, tesofensine administration resulted in appetite suppression and weight loss with reversal of low forebrain dopamine levels. [17-18]
  13. In a rat model of diet-induced obesity (DIO), administration of tesofensine (2.0 mg/kg, s.c.) for 16 days significantly reduced body weights. [19]
  14. In diet-induced obese rats, tesofensine treatment at 2 mg/kg for 28 days decreased food intake and body weight. [20]
  15. In 203 obese persons, tesofensine 0.5 mg produced a weight loss twice that of currently approved anti-obesity drugs. [21]

Improves Cognitive Health

Research indicates that tesofensine helps preserve cognitive health by indirectly potentiating cholinergic neurotransmission, which is a process wherein nerve cells relay messages to each other. [22] This has been proven to have beneficial effects on various areas of cognitive health, including learning, memory, and thinking skills. The following studies support this effect:

  1. First clinical results of two small 4-week phase IIa trials performed in patients with mild Alzheimer’s disease (AD) showed that tesofensine treatment induced significant improvement in cognitive function. [23-24]
  2. A growing body of research indicates that obesity is a major risk factor for cognitive impairment especially in the older population. [25-28] With its anti-obesity effect, tesofensine may help protect against cognitive impairment.
  3. In a mouse model of Alzheimer’s disease, tesofensine administration decreased the brain concentrations of amyloid beta, which are abnormal protein aggregates and is the causative agent of the disease. [29]
  4. In patients with advanced Parkinson’s disease and motor fluctuations, low-dose tesofensine improved activities of daily living and motor function. [30]

Improves Mood

Sustained treatment with tesofensine has been shown to improve overall mood through its antidepressant effect. Studies show that tesofensine affects mood by:

  1. Increasing the levels of brain-derived neurotrophic factor (BDNF), thereby triggering an antidepressant effect. [31]
  2. Triggering an anti-anxiety effect in obese patients with comorbid depression and anxiety symptoms. [32]
  3. Increasing the levels of the neurotransmitters serotonin, noradrenaline, and dopamine. [33]

Improves Blood Sugar Levels

Tesofensine has also been found to have beneficial effects on blood sugar. Studies show that:

  1. In obese patients, administration of tesofensine at varying doses (0.25 mg, 0.5 mg, and 1.0 mg) resulted in significant reduction in blood sugar levels and improvement in quality of life. [34]
  2. In rodents, tesofensine also induced a significant reduction in blood sugar levels in addition to weight loss. [35-36]

Increases Energy Levels

Tesofensine treatment is also beneficial in improving one’s productivity by increasing energy levels. In one study, administration of tesofensine in overweight and moderately obese men induced higher energy expenditure compared to placebo. [37]

Treats Sexual Dysfunction

Because of its potent antidepressant effect, tesofensine has also been studied for its therapeutic benefits on sexual dysfunction. Studies show that tesofensine administration is effective in treating depression-related sexual dysfunction, [38] suggesting that it can help ramp up sexual power.

Treats Eating Disorders

Triple reuptake inhibitor such as tesofensine also holds therapeutic potential for eating disorders. In patients with binge eating disorder, a condition in which a person eats large quantities of food when stressed, tesofensine administration has been shown to improve its symptoms, possibly due to tesofensine’s potent antidepressant effect. [39-42]

Treats Attention-Deficit/Hyperactivity Disorder (ADHD)

ADHD is characterized by short attention span, hyperactivity and impulsivity, and is common in children and even adults. Studies show that this mental disorder is strongly linked with low levels of dopamine and serotonin. [43-45] Since tesofensine’s mode of action is that it increases the levels of these neurotransmitters, this drug may help reduce the symptoms of ADHD.

Improves Sleep Quality

A deficiency in the neurotransmitter serotonin has been linked to insomnia and various sleeping difficulties, according to studies. [46-50] On the other hand, increasing the levels of serotonin through selective serotonin reuptake inhibitors treatment has been shown to improve objective and subjective sleep quality in patients with sleeping difficulties. [51-53] With tesofensine’s ability to boost serotonin levels, it may have a positive effect on sleep quality, pattern, and duration.

Fights Alcohol Addiction

Studies show that low dopamine levels are associated with alcohol addiction. [54-57] With tesofensine’s ability to increase dopamine levels, it may help reduce excessive alcohol intake along with its symptoms. Animal studies even found that in ethanol-preferring rats, triple reuptake inhibitor administration reduced alcohol consumption without decreasing food or water consumption. [58]


  1. Mahapatra A. Overeating, Obesity, and Dopamine Receptors. ACS Chemical Neuroscience. 2010;1(5):346-347. doi:10.1021/cn100044y. Retrieved from
  2. Blum K, Thanos PK, Gold MS. Dopamine and glucose, obesity, and reward deficiency syndrome. Frontiers in Psychology. 2014;5:919. doi:10.3389/fpsyg.2014.00919. Retrieved from
  3. Karlsson HK, Tuominen L, Tuulari JJ. Obesity is associated with decreased μ-opioid but unaltered dopamine D2 receptor availability in the brain. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015; 35(9):3959-65. Retrieved from
  4. Wang GJ, Volkow ND, Logan J. Brain dopamine and obesity. Lancet (London, England). 2001; 357(9253):354-7. Retrieved from
  5. Benton D, Young HA. A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction? International Journal of Obesity (2005). 2016;40(Suppl 1):S12-S21. doi:10.1038/ijo.2016.9. Retrieved from
  6. Retrieved from
  7. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2008; 372(9653):1906-1913. Retrieved from
  8. Retrieved from
  9. Retrieved from
  10. Retrieved from
  11. Doggrell SA. Tesofensine–a novel potent weight loss medicine. Evaluation of: Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1906-13. Expert opinion on investigational drugs. 2009; 18(7):1043-6. Retrieved from
  12. Gilbert JA, Gasteyger C, Raben A, Meier DH, Astrup A, Sjödin A. The effect of tesofensine on appetite sensations. Obesity (Silver Spring, Md.). 2012; 20(3):553-61. Retrieved from
  13. Bello NT, Zahner MR. Tesofensine, a monoamine reuptake inhibitor for the treatment of obesity. Current opinion in investigational drugs (London, England : 2000). 2009; 10(10):1105-16. Retrieved from
  14. Retrieved from
  15. Astrup A, Meier DH, Mikkelsen BO, Villumsen JS, Larsen TM. Weight loss produced by tesofensine in patients with Parkinson’s or Alzheimer’s disease. Obesity (Silver Spring, Md.). 2008; 16(6):1363-9. Retrieved from
  16. Appel L, Bergström M, Buus Lassen J, Långström B. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2014; 24(2):251-61. Retrieved from
  17. Hansen HH, Jensen MM, Overgaard A, Weikop P, Mikkelsen JD. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat. Pharmacology, biochemistry, and behavior. 2013; 110:265-71. Retrieved from
  18. Lehr T, Staab A, Tillmann C, et al. Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach. Br J Pharmacol. 2008;153(1):164–174. doi:10.1038/sj.bjp.0707539. Retrieved from
  19. Axel AM, Mikkelsen JD, Hansen HH. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat. Neuropsychopharmacology. 2010;35(7):1464-76. Retrieved from
  20. Van de giessen E, De bruin K, La fleur SE, Van den brink W, Booij J. Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats. Eur Neuropsychopharmacol. 2012;22(4):290-9. Retrieved from
  21. Nielsen AL, Larsen TM, Madsbad S, et al. [The effect of tesofensine on body weight and body composition in obese subjects–secondary publication]. Ugeskr Laeg. 2009;171(41):2974-7. Retrieved from
  22. Retrieved from
  23. Thatte U. NS-2330 (Neurosearch). Current opinion in investigational drugs (London, England : 2000). 2001; 2(11):1592-4. Retrieved from
  24. Lehr T, Staab A, Trommeshauser D, Schaefer HG, Kloft C. Quantitative Pharmacology Approach in Alzheimer’s Disease: Efficacy Modeling of Early Clinical Data to Predict Clinical Outcome of Tesofensine. The AAPS Journal. 2010;12(2):117-129. doi:10.1208/s12248-009-9164-6. Retrieved from
  25. Elias M. F., Elias P. K., Sullivan L. M., Wolf P. A., D’Agostino R. B. (2005). Obesity, diabetes and cognitive deficit: the Framingham heart study. Neurobiol. Aging 26 Suppl.1, 11–16. 10.1016/j.neurobiolaging.2005.08.019. Retrieved from
  26. Jeong S. K., Nam H. S., Son M. H., Son E. J., Cho K. H. (2005). Interactive effect of obesity indexes on cognition. Dement. Geriatr. Cogn. Disord. 19, 91–96. 10.1159/000082659. Retrieved from
  27. Hassing L. B., Dahl A. K., Pedersen N. L., Johansson B. (2010). Overweight in midlife is related to lower cognitive function 30 years later: a prospective study with longitudinal assessments. Dement. Geriatr. Cogn. Disord. 29, 543–552. 10.1159/000314874. Retrieved from
  28. Cournot M., Marquie J. C., Ansiau D., Martinaud C., Fonds H., Ferrieres J., et al. . (2006). Relation between body mass index and cognitive function in healthy middle-aged men and women. Neurology 67, 1208–1214. 10.1212/01.wnl.0000238082.13860.50. Retrieved from
  29. Tesofensine, a monoamine reuptake inhibitor for the treatment of obesityBornemann KD, Rosenbrock H, Sams-Dodd F. Amyloid β-lowering activity of the neurotransmitter reuptake inhibitor NS 2330 in vitro and in an APP transgenic mouse model. 2006, submitted.
  30. Rascol O, Poewe W, Lees A, et al. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study. Arch Neurol. 2008;65(5):577-83. Retrieved from
  31. Larsen MH, Rosenbrock H, Sams-Dodd F, Mikkelsen JD. Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine. European journal of pharmacology. 2007; 555(2-3):115-21. Retrieved from
  32. Nathan PJ, O’Neill BV, Napolitano A, Bullmore ET. Neuropsychiatric adverse effects of centrally acting antiobesity drugs. CNS neuroscience & therapeutics. 2011; 17(5):490-505. Retrieved from
  33. Marks DM, Pae C-U, Patkar AA. Triple Reuptake Inhibitors: The Next Generation of Antidepressants. Current Neuropharmacology. 2008;6(4):338-343. doi:10.2174/157015908787386078. Retrieved from
  34. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2008; 372(9653):1906-1913. Retrieved from
  35. George M, Rajaram M, Shanmugam E. New and emerging drug molecules against obesity. Journal of cardiovascular pharmacology and therapeutics. 2014; 19(1):65-76. Retrieved from
  36. Hansen HH, Hansen G, Tang-Christensen M. The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant. European journal of pharmacology. 2010; 636(1-3):88-95. Retrieved from
  37. Sjödin A, Gasteyger C, Nielsen AL. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. International journal of obesity (2005). 2010; 34(11):1634-43. Retrieved from
  38. Marks DM, Pae CU, Patkar AA. Triple reuptake inhibitors: a premise and promise. Psychiatry investigation. 2008; 5(3):142-7. Retrieved from
  39. Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, Weyer C. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes care. 2008; 31(9):1816-23. Retrieved from
  40. Fong TM. Development of anti-obesity agents: drugs that target neuropeptide and neurotransmitter systems. Expert opinion on investigational drugs. 2008; 17(3):321-5. Retrieved from
  41. Fidler MC, Sanchez M, Raether B. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. The Journal of clinical endocrinology and metabolism. 2011; 96(10):3067-77. Retrieved from
  42. Smith SR, Weissman NJ, Anderson CM. Multicenter, placebo-controlled trial of lorcaserin for weight management. The New England journal of medicine. 2010; 363(3):245-56. Retrieved from
  43. Sharma H, Santra S, Dutta A. Triple reuptake inhibitors as potential next-generation antidepressants: a new hope? Future Medicinal Chemistry. 2015;7(17):2385-2405. doi:10.4155/fmc.15.134. Retrieved from
  44. Gold MS, Blum K, Oscar-Berman M, Braverman ER. Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children? Postgraduate medicine. 2014;126(1):153-177. doi:10.3810/pgm.2014.01.2735. Retrieved from
  45. Oades RD. Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD). Progress in brain research. 2008; 172:543-65. Retrieved from
  46. Vashadze ShV. [Insomnia, serotonin and depression]. Georgian medical news. 2007. Retrieved from
  47. McGinty DT. Serotonin and Sleep: Molecular, Functional, and Clinical Aspects. Sleep. 2009;32(5):699-700. Retrieved from
  48. Whitney MS, Shemery AM, Yaw AM, Donovan LJ, Glass JD, Deneris ES. Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2016; 36(38):9828-42. Retrieved from
  49. Pakalnis A, Splaingard M, Splaingard D, Kring D, Colvin A. Serotonin Effects on Sleep and Emotional Disorders in Adolescent Migraine. Headache. 2009;49(10):1486-1492. doi:10.1111/j.1526-4610.2009.01392.x. Retrieved from
  50. Murray NM, Buchanan GF, Richerson GB. Insomnia Caused by Serotonin Depletion is Due to Hypothermia. Sleep. 2015; 38(12):1985-93. Retrieved from
  51. Oberndorfer S, Saletu-Zyhlarz G, Saletu B. Effects of selective serotonin reuptake inhibitors on objective and subjective sleep quality. Neuropsychobiology. 2000; 42(2):69-81. Retrieved from
  52. Aarts N, Zuurbier LA, Noordam R. Use of Selective Serotonin Reuptake Inhibitors and Sleep Quality: A Population-Based Study. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2016; 12(7):989-95. Retrieved from
  53. Saltiel PF, Silvershein DI. Major depressive disorder: mechanism-based prescribing for personalized medicine. Neuropsychiatric Disease and Treatment. 2015;11:875-888. doi:10.2147/NDT.S73261. Retrieved from
  54. MA H, ZHU G. The dopamine system and alcohol dependence. Shanghai Archives of Psychiatry. 2014;26(2):61-68. doi:10.3969/j.issn.1002-0829.2014.02.002. Retrieved from
  55. Banerjee N. Neurotransmitters in alcoholism: A review of neurobiological and genetic studies. Indian Journal of Human Genetics. 2014;20(1):20-31. doi:10.4103/0971-6866.132750. Retrieved from
  56. Noble EP. Alcoholism and the dopaminergic system: a review. Addiction biology. 1996; 1(4):333-48. Retrieved from
  57. Di Chiara G. Alcohol and dopamine. Alcohol health and research world. 1997; 21(2):108-14. Retrieved from
  58. McMillen BA, Shank JE, Jordan KB, Williams HL, Basile AS. Effect of DOV 102,677 on the volitional consumption of ethanol by Myers’ high ethanol-preferring rat. Alcoholism, clinical and experimental research. 2007; 31(11):1866-71. Retrieved from
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